Stroke May Boost Alzheimer's Risk

Finding could lead to future treatment for the disease

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HealthDay Reporter

MONDAY, Dec. 15, 2003 (HealthDayNews) -- Two new studies shed light on important risk factors for Alzheimer's disease and on a possible future therapy for the disease.

The first found people who have suffered a stroke are at a higher risk for developing this dementia; that risk is higher still if the person also has cardiovascular disease.

The second suggests chelation therapy, which involves binding metals in the body, lowers levels of beta amyloid in people with Alzheimer's. Aggregations of this protein in the brain are a hallmark of the disease. The 36 patients in this study who took the drug clioquinol experienced some improvement in cognitive function.

Both studies, which appear in the December issue of the Archives of Neurology, represent potentially important advances in experts' understanding of Alzheimer's. Thus far, the only available treatments are those that have a mild effect on symptoms, and nothing that impacts the underlying disease process.

Clinicians traditionally divide dementia patients into two broad categories -- vascular dementia (brought on by problems with blood circulation to the brain) and degenerative dementia (usually meaning Alzheimer's). The problem is that many cases of dementia seem to overlap the two categories, says Dr. Sam Gandy, vice president of the Alzheimer's Association's Medical and Scientific Advisory Council.

"[The new research] begins to revise our thinking because, if this is a continuum of one disease, then they could be thought of that way in designing new therapies," says Gandy, who also is director of the Farber Institute for Neurosciences at Thomas Jefferson University in Philadelphia.

"It is a really solid study to try to revolutionize or revamp the way doctors diagnose, and, more importantly for the patients, eventually develop treatments for dementia," he says. It may be possible that one therapy could attack both problems.

In the first study, Columbia University investigators looked at 1,766 Medicare patients aged 65 and older who did not have dementia or Alzheimer's disease at the start of the trial. Some of the participants had had a stroke or other cardiovascular risk factors.

Over the course of seven years, the annual incidence of Alzheimer's was 5.2 percent among patients who suffered a stroke and 4 percent among those who didn't. Hypertension, diabetes and heart disease made the risk even higher. People with a history of stroke also tended to get Alzheimer's earlier.

"The coexistence suggests that one is probably increasing the risk for the other," Gandy says.

The theory behind the second study is that metals in the brain -- specifically copper and zinc -- are responsible for the aggregation of beta amyloid.

"We first worked in a test tube to discover that beta amyloid has an unusual vulnerability to reaction with zinc and copper," explains study co-author Dr. Ashley Bush, an associate professor of psychiatry at Massachusetts General Hospital and Harvard Medical School. "Then we found we could stop the reactions with chemicals that pluck metal out from the protein. That sort of chemical is called a chelator."

Earlier research had found a compound called clioquinol dissolved beta amyloid clusters in test tubes, in mice and in the brain tissues of deceased Alzheimer's patients.

The new study marked the first test of the theory in humans. It was a clinical trial of clioquinol in 36 patients with "moderately severe" Alzheimer's. Clioquinol, Bush notes, is a "retired antibiotic" that has not been used in decades.

Half of the participants received daily doses of the compound while the other half received a placebo for 36 weeks.

At the end of the trial, patients who were taking clioquinol had lower blood levels of beta amyloid and also scored slightly better on tests of cognitive ability.

"It does seem to have promising effects in arresting deterioration," Bush says. "This is like first base in the progress towards taking this drug to the clinic." If the drug passes the myriad other tests it faces, Bush envisions it being used as both prevention and treatment for Alzheimer's if the disease can be diagnosed early enough.

Chelation therapy for Alzheimer's is still a long way off, if it ever materializes. "In a small trial there is a modest stabilization of cognitive decline at one point in time so it's tantalizing but preliminary," Gandy says. "I wouldn't say that people should start clamoring for this."

Still, Gandy himself will try to replicate these findings using clioquinol in a trial involving 80 patients in the United States. The results of this and other studies may help answer one of the enduring mysteries in Alzheimer's research.

William Thies, vice president of medical and scientific affairs at the Alzheimer's Association, says, "If amyloid 'plaque-buster' drugs are effective in preventing or treating Alzheimer's, this may solve the longstanding, often heated controversy surrounding the issue of whether amyloid really causes Alzheimer's or is instead an innocent bystander.

"A positive result would lead to a redoubled effort at more and better 'anti-amyloid' medicines. A negative result will send the world's Alzheimer experts back to 'square one,' " Thies says.

More information

For more on Alzheimer's, visit the Alzheimer's Association and the National Institute on Aging.

SOURCES: Sam Gandy, M.D., Ph.D., vice president, Medical and Scientific Advisory Council, Alzheimer's Association, and director, Farber Institute for Neurosciences, Thomas Jefferson University, Philadelphia; Ashley Bush, M.D., Ph.D., associate professor, psychiatry, Massachusetts General Hospital and Harvard Medical School, both in Boston; statement from William Thies, Ph.D., vice president, medical and scientific affairs, Alzheimer's Association, Chicago; December 2003 Archives of Neurology

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